IMPACT OF FAMILY HISTORY OF CRC ON ADENOMAS IN 40-49 YEAR OLDS BACKGROUND: The goal of CRC screening is to prevent cancer by identifying and removing advanced pre- cancerous polyps (i.e., advanced adenomas defined as adenomas > 10 mm, villous adenomas, adenomas with high-grade dysplasia) during colonoscopy. Current guidelines from academic societies and VA Directives provide different recommendations about the need to perform colonoscopy in 40-49 year olds with a family history of CRC in a first-degree relative (FDR). We hypothesize that 40-49 year old individuals with a family history of CRC will have an increased risk of advanced adenoma compared to age-matched controls. OBJECTIVES: (A) To estimate the absolute prevalence of advanced adenomas among 40-49 year old individuals with a family history of CRC and to compare this absolute prevalence versus the absolute prevalence of advanced adenomas in 40-49 year old average-risk individuals with scant hematochezia, abdominal discomfort, or altered bowel habits (i.e., constipation or diarrhea) as their indication for colonoscopy; (B) Identify risk factors associated with advanced adenomas or adenomas (any size) among 40-49 year old individuals with a family history of CRC using multiple logistic regression analysis. METHODS: This is a multi-center, prospective cohort study conducted at four sites (Ann Arbor VAHS, Durham VAHS, U. of Michigan Health System, and the National Naval Medical Center, Bethesda, MD). Inclusion criteria: 40-49 year old asymptomatic individuals referred for colonoscopy due to a family history of CRC AND 40-49 year old individuals without a family history of CRC or colon polyps who are referred for colonoscopy to evaluate scant hematochezia, abdominal discomfort or altered bowel habits. [Note: Although performance of colonoscopy is the standard of care to evaluate these symptoms, the presence of these symptoms is NOT associated with an increased risk of advanced adenomas in 40-49 year olds. Therefore, colonoscopy can be justified in these patients AND these patients represent an average-risk population for advanced adenomas.] After obtaining informed consent from study patients, we will gather data on the size, morphology, and location of polyps from colonoscopy report forms and polyp pathology reports. Study patients will also complete a risk factor survey for adenomas which has been adapted from a National Cancer Institute survey. Patient self-report of family history of CRC will be used since published literature demonstrates 86-93% sensitivity and 92-100% specificity for self-report of this family history. Sample size for this study has been set at 1940 patients which will be sufficient to quantify a relative risk of 2.0 for advanced adenomas in 40-49 year old individuals with a family history of CRC if the absolute prevalence of advanced adenomas is at least 4.0%. Pilot funding has been obtained, and patient recruitment has already been initiated at two sites. On August 31, 2009, 160 patients had been enrolled and recruitment has increased to 7-8 patients per week. PUBLIC HEALTH RELEVANCE: 7.9 million Veterans receive health care in the VA. Approximately 10% or 790,000 have a first-degree relative (FDR) with colorectal cancer (CRC). Should any of these patients undergo colonoscopy at age 40 due to an increased prevalence of advanced adenomas? There is not adequate prospective data in 40-49 year olds with this family history to answer this question. Guidelines provide conflicting recommendations about performing colonoscopy at age 40 or 50 in these patients, but guidelines emphasize that prospective data are needed to clarify recommendations. The 2007 VA CRC Directive states that individuals with a FDR with CRC <60 years old are to get colonoscopy at age 40, but individuals with a FDR with CRC > 60 may get colonoscopy at age 40. VA endoscopic resources are limited. This study will determine if hundreds of thousands of Veterans should get colonoscopy starting at age 40 or age 50.